Cord Blood: Biological Insurance or Gimmick?‎

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Almost all maternity patients receive proposals to preserve fetal cord blood for a ‎great amount of money, with the promise of the possibility to cure many diseases ‎in the future. Is all the hype true? What can be done with cord blood and what are ‎the disadvantages of the treatment? Also – what are the public repercussions of ‎the method?‎

Young parents nowadays are faced with many issues arising from technological developments and the availability of information on the Internet. Should they vaccinate their children? Is it possible to give up breast-feeding? Should they buy organic food? What about genetically modified food?

In recent years the new trend causing a dilemma is whether to preserve umbilical cord blood for private use? Today cord blood is already being used to treat dozens of blood diseases, such as primary immunodeficiency ("bubble children"), blood cancers and certain types of anemia. Commercial companies now offer, with often-aggressive advertising, paid preservation of cord blood for personal or family use. Beyond available treatments, the companies promise frozen cord blood will be used in the future to treat disorders such as autism and cerebral palsy.

Like other medical issues, cord blood preservation is a complex subject and the whole field is still evolving. This article will present the latest scientific findings and shed some light on how cord blood is currently being used in the field.

Cord blood is the blood collected at birth from the umbilical cord and placenta - the tissues that feed the fetus and connect it to its mother. Cord blood has been a focus for the last thirty years of research because it is rich in stem cells, which can develop into a wide variety of cells throughout the body. Cord blood is rich mainly in Hematopoietic stem cells that develop into the different blood cells, which are vital for treating various blood diseases. Many of these diseases are treated with bone marrow transplants because bone marrow contains these blood-forming stem cells that are capable of replacing the defective stem cells of the patient.

In order to successfully transplant blood-forming stem cells one requires a match between a donor and recipient. The mismatched recipient may reject the implant or the implant itself might attack the recipient's body - as so often happens when transplanting bone marrow in blood cancer patients.

Blood engraftment depends on “matching” genes known as HLA, which mark the differences between the body's own cells and foreign cells. Each person has six copies of these genes, and in order to be able to conduct a successful transplant a maximal match is required between all six copies of the donor and the transplant patient – a statistically rare combination. Without a match, the T cells of the immune system will recognize the graft or the body of the recipient as foreign and attack it. If the implant matches only four or five copies of HLA, its engraftment can be problematic.

A fight against the numbers

The great advantage of cord blood over bone marrow transplantation lies in the fact that it produces a weaker rejection response. Cord blood T cells are younger and less "experienced" and therefore more "promiscuous" than those of adult bone marrow so their attack on the "alien" body is gentler. When a matching HLA donor cannot be found even among the patient’s relatives, the dose can be transplanted from cord blood; the engraftment will be "milder" than when matched with a less than optimal donor.

Another advantage of cord blood is that it contains not only the blood-forming stem cells, but also Mesanchymal stem cells, which develop into cells that are not within the blood system such as bone, fat, heart and cartilage cells. But as we shall see, successful results are not yet prevalent.

A significant disadvantage of cord blood cells is the tiny amount that exists compared to that in a bone marrow dose. Researchers estimate that a single dose of cord blood that contains approximately 900 million cells can be used to treat children, whereas adults probably need several doses. Today, attempts are being made to increase the number of blood-forming stem cells within cord blood, so that one dose will be enough even for an adult. For example, the company Gamida Cell recently announced it has developed a breakthrough product for this purpose, but it is still currently under development.

A brief history

"Cord blood transplants account for about five to ten percent of the world's stem cell transplants. Israel performs about 10-15 such transplants per year", says Professor Isaac Yaniv, Head of Hematology-Oncology at Schneider Children’s Hospital. "When a patient needs a transplant as part of treatment for a blood disease, cord blood is the third priority because of the slow recovery and we have much more experience with bone marrow transplantation.

"First of all we are looking for a donation from a sibling, because there is a twenty-five percent chance to have a full HLA match. If there are no matches or no siblings, we look on our bone marrow donor database or for an ordinary blood donation (i.e. peripheral blood), while at the same time we also look for a cord blood donation. Whenever it comes to diseases of blood, cord blood becomes a very effective resource due to high availability of public databases. Sometimes there is not enough time to find a suitable bone marrow donor, and because a cord blood match is less stringent, it is preferable".

The idea of ​​using cord blood to treat diseases was first conceived by Professor Hal Broxmeyer in the early 1980s. The first cord blood transplant was done in France in 1988 on an American boy who suffered from Fanconi anemia. His mother had just given birth to a baby girl who had a complete HLA match to the sick child, and the new sister was not a carrier of the disease. Due to the urgency of the transplant and the inability to take the new baby’s bone marrow, Broxmeyer took the baby's cord blood and flew to Paris with the sick child and the frozen cord blood. He also needed to buy a full priced plane ticket for a seat for the cooler that held the specimen.

In France Prof. Eliane Gluckman completed the transplant. The first experiment of its kind was successful and the recipient lives today as a healthy individual. Since then there have been around thirty thousand transplants worldwide, with the vast majority being foreign donors rather than family members. Over the last three decades the results from using umbilical cord blood have greatly improved thanks to a better selection of patients and cord blood samples, and the proportion of patients who survive the transplant is constantly increasing.

Private or public

The question of whether to preserve cord blood in a private bank is complex and multi-layered. One of the main reasons to store in a private bank is a chance to carry out autologous transplants (using one’s own stem cells). But most blood diseases, including blood cancers, are discovered in early childhood and are due to a genetic defect, so cord blood cells will carry the defect and the implant will not help the patient.

According to the most up-to-date scientific and medical knowledge, the chances of being able to use one’s own cord blood for a transplant is very low. In 2008 a committee for the American Society of Blood and Marrow Transplantation estimated that the chances of such a transplant is between 1:2500 to 1:200,000 only. It is recommended to encourage cord blood for use within a family only if a family member has a relevant blood disorder. However, according to other estimates the chances for a successful transplant are considerably higher. An article responded against the position of the American Society estimating that the chance is actually 1:400 in adult patients. Although it is important to note there are only very few reports in the literature on the use of autologous cord blood in blood cancers.

Transplantation when not used on oneself has a twenty-five percent chance of being a match for siblings. Therefore, young parents could ask themselves if they want to invest in a particular insurance that is only useful for genetic blood disease, and where the chance of success is about twenty-five percent.

"Childhood leukemia already develops while in the womb and so cord blood cells also have leukemia", explains Prof. Yaniv. "It has happened quite a few times where parents of a sick child with leukemia are pleased they have preserved cord blood, and I have to explain to them that it cannot be used. The only situation in which I would recommend a transplant for family use is in the case of a sick child whose mother is pregnant. In this case we want to freeze the cord blood of the sibling to see if they are a suitable donor. If so, this cord blood can be saved for only two years. After this time we already prefer to use a sibling bone marrow donor, thanks to a more rapid recovery from the procedure. Just this year, this short-term preservation was added to the standard health insurance basket".

Private storage advocates argue that despite the low probability of self-transplant, the stem cells will provide a tremendous therapeutic potential that is still untapped, for example treating diseases such as cerebral palsy, diabetes, autism and Parkinson's. According to these camps, private storages of cord blood will be ready for regular use in the near future with significant health benefits to those who prepared with such insurance.

Although it is quite possible, it is obvious that private banks raise these arguments with aggressive marketing campaigns because they have an interest in promoting the subject. Despite the encouraging experiments in these areas, and despite cases in which autologous transplant of umbilical cord blood has improved the condition of patients - for example in cerebral palsy (here, here and here), these successes are still very rare and treatments are only at their first steps. After all, who is going to show a YouTube video for a patient whose situation has not improved, or even worsened following a transplant?

Treatments and knowledge are still at their first steps. Cord blood bank | Photo: Science Photo Library

"No one today can know if stem cells will be used to treat diseases that are not blood disorders, such as autism," says Prof. Zvi Lapidot of the Immunology Department at the Weizmann Institute of Science, an expert in hematopoietic stem cells. "Blood-forming stem cells have a remarkable feature - once they are injected into the blood they know to return to their niches in the bone marrow and differentiate into various blood cells. Other stem cells do not know how to do this and hence there lies the great difficulty in working with them to get good results."

Prof. Lapidot stressed that despite progress in stem cell research, there is a long way to go before their clinical use. "Human embryonic stem cells are able to differentiate into any cell of the body, and this was discovered nearly twenty years ago, and the technology to of creating stem cells from adult cells has existed for ten years, but these developments have not saved even one person yet. Perhaps in the future it will be possible, but we won’t see this any time soon. So I’m not sure that anyone who preserves cord blood today for personal use, aside for blood diseases, could benefit from it. This technology might evolve in a few decades, if ever. The claim that in the future cord blood might possibly cure autism, for example, is nothing but a commercial marketing ploy."

Currently the consensus of scientific-medical centers is that one is encouraged to store cord blood in public banks, and not privately, with the rationalization that family or personal use of such blood is very unlikely. This position is supported by other organizations such as the American Society of Blood and Marrow Transplantation, estimating that the chance to use cord blood stored at a public bank is one hundred times greater than compared to a sample that is stored in a private bank. The American Academy of Pediatrics, the American Congress of Obstetricians and Gynecologists and the World Marrow Donor Association also agree on this. There is a considerable difference between private banks that present cord blood preservation as “biological insurance'', and the concept of scientific-medical establishments that see cord blood as a "long term investment" that might or might not justify itself in the future.

Quality control

Another issue is the "life span" and quality of cord blood throughout its preservation. Studies have shown that stem cells from cord blood are still able to generate blood cells and other cells from cord blood stored twenty years ago. However, banks have only existed for a little more than two decades so nobody knows what will be the quality of the sample after a longer period. It also depends on the quality of the sample when it is actually taken.

According to the Israeli practice of private banks, they are not committed to any such threshold. "We know for sure of samples preserved in private banks that do not contain the minimum amount necessary for a transplant," says Prof. Yaniv.

Most cord blood samples that do not meet the threshold conditions for preservation in public banks are donated to science. However, samples kept in private banks cannot be donated to science without the consent of the family, even if they are unusable for transplantation. If all cord blood donors were storing in private banks, research would come to a complete halt, even though future use of cord blood depends entirely on this research.

Public interest

Another important aspect is the public’s responsibility for storage. Someone who preserves the umbilical cord blood of their children for personal use is like a person who wants to donate his organs after his death only for his family, and not for the general public. This has many implications, such as the availability of cord blood to ethnic minorities. Most bone marrow donors in the western world are white, and therefore ethnic minorities find it harder to find a bone marrow donor. The option to settle for only partially genetically matched cord blood donations increases the chances for minorities to be able to receive donations.

"The state should invest in the representation and participation of ethnic minorities such as Arabs, Bedouins, Bukharis, Yemenites and Ethiopians – in both cord blood banks and bone marrow banks," says Prof. Yaniv. "All of these minorities have difficulty finding donors and there is no point in continuing to collect donations of Ashkenazi Jews who are well represented in the storages. Among the Arab population, for example, there is strong opposition to donation to reservoirs, so public relations work needs to be done here."

A fundamental need

Perhaps from some of the aforementioned, a negative image has emerged regarding private banks as allegedly misleading the public and selling misconceptions, as expressed by former Health Ministry Director-General Dr. Ronni Gamzu. Of course the truth is more complex, and these banks need to find a real need to sell to the public. The amount of storage of cord blood in public banks in Israel reaches several hundred packets a year. In 2011 such banks had about 8,000 cord blood samples, and if we take into account that for many cases two blood samples are required for transplantation, very few patients will be able to benefit from the contribution.

For years, public banks were funded by donations. Only in 2007 the cord blood bill, initiated by Knesset Member Moshe Kahlon, was passed, and only in 2010 was the law implemented, following lobbying by Knesset Member Zeev Bielski, where public banks activity was allocated a budget of three million NIS a year.

As mentioned above, in Israel there is a fundamental need for a variety of donations of umbilical cord blood because of the many ethnic minorities that are not represented in the reservoirs, and therefore their difficulty in receiving donations. Entering this vacuum are the private companies, together with parents who fear that the state will not care for their children when necessary. This is a life-saving channel that the country should invest more in, rather than shifting the decision and the responsibility onto the parents themselves.